Molecular tweaking by generative cheminformatics and ligand–protein structures for rational drug discovery

The importance of structure-guided-drug design through collaboration of synthetic and medicinal chemistry with structural biology and artificial intelligence is presented as an accelerated drug discovery platform. [Display omitted] The purpose of this review is two-fold: (1) to summarize artificial intelligence and machine learning approaches and document the role of ligand–protein structures in directing drug discovery; (2) to present examples of drugs from the recent literature (past decade) of case studies where such strategies have been applied to accelerate the discovery pipeline. Compared to 50 years ago when drug discovery was largely a synthetic chemist driven research exercise, today a holistic approach needs to be adopted with seamless integration between synthetic and medicinal chemistry, supramolecular complexes, computations, artificial intelligence, machine learning, structural biology, chemical biology, diffraction analytical tools, drugs databases, and pharmacology. The urgency for an integrated and collaborative platform to accelerate drug discovery in an academic setting is emphasized.